Association of KRAS G13D Tumor Mutations With Outcome in Patients With Metastatic Colorectal Cancer Treated With First-Line Chemotherapy With or Without Cetuximab
作者： Sabine Tejpar , Ilhan Celik , Michael Schlichting , Ute Sartorius , Carsten Bokemeyer
关键词: Proportional hazards model 、 Medicine 、 KRAS 、 Survival analysis 、 Colorectal cancer 、 Odds ratio 、 Oncology 、 Internal medicine 、 Cetuximab 、 Hazard ratio 、 Chemotherapy
摘要: Purpose We investigated in the first-line setting our previous finding that patients with chemorefractory KRAS G13D‐mutated metastatic colorectal cancer (mCRC) benefit from cetuximab treatment. Methods Associations between tumor mutation status (wild-type, G13D, G12V, or other mutations) and progression-free survival (PFS), survival, response were pooled data 1,378 evaluable CRYSTAL OPUS studies. Multivariate analysis correcting for differences baseline prognostic factors was performed. Results Of 533 (39%) KRAS-mutant tumors, 83 (16%) had 125 (23%) 325 (61%) mutations. Significant variations treatment effects found (P .005) PFS (P.046) G13D-mutant tumors versus all mutations (including G12V). Within subgroups, plus chemotherapy alone significantly improved (median, 7.4 v 6.0 months; hazard ratio [HR], 0.47; P .039) (40.5% 22.0%; odds ratio, 3.38; .042) but not 15.4 14.7 HR, 0.89; .68) tumors. Patients G12V did this combination. receiving experienced worse outcomes (response, 22.0% 43.2%; 0.40; .032) than those Effects similar separate Conclusion The addition of to seems G13D‐mutant Relative wild-type lower absolute values. J Clin Oncol 30. © 2012 by American Society Clinical Oncology
researchgate.net 
sci-hub.se 参考文章(31)
Gabriel Capellà, Lourdes Farré, Isolda Casanova, Adela Mazo, Sílvia Guerrero, Ramon Mangues, K-ras codon 12 mutation induces higher level of resistance to apoptosis and predisposition to anchorage-independent growth than codon 13 mutation or proto-oncogene overexpression. Cancer Research. ,vol. 60, pp. 6750- 6756 ,(2000)
Wendy De Roock, Derek J. Jonker, Federica Di Nicolantonio, Andrea Sartore-Bianchi, Dongsheng Tu, Salvatore Siena, Simona Lamba, Sabrina Arena, Milo Frattini, Hubert Piessevaux, Eric Van Cutsem, Chris J. O’Callaghan, Shirin Khambata-Ford, John R. Zalcberg, John Simes, Christos S. Karapetis, Alberto Bardelli, Sabine Tejpar, Association of KRAS p.G13D Mutation With Outcome in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer Treated With Cetuximab JAMA. ,vol. 304, pp. 1812- 1820 ,(2010) , 10.1001/JAMA.2010.1535
Inti Zlobec, Michal Kovac, Priska Erzberger, Francesca Molinari, Michel P. Bihl, Alexander Rufle, Anja Foerster, Milo Frattini, Luigi Terracciano, Karl Heinimann, Alessandro Lugli, Combined analysis of specific KRAS mutation, BRAF and microsatellite instability identifies prognostic subgroups of sporadic and hereditary colorectal cancer. International Journal of Cancer. ,vol. 127, pp. 2569- 2575 ,(2010) , 10.1002/IJC.25265
T Yokota, T Ura, N Shibata, D Takahari, K Shitara, M Nomura, C Kondo, A Mizota, S Utsunomiya, K Muro, Y Yatabe, BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer British Journal of Cancer. ,vol. 104, pp. 856- 862 ,(2011) , 10.1038/BJC.2011.19
Christian V. Recktenwald, Simone Mendler, Rudolf Lichtenfels, Roland Kellner, Barbara Seliger, Influence of Ki-ras-driven oncogenic transformation on the protein network of murine fibroblasts. Proteomics. ,vol. 7, pp. 385- 398 ,(2007) , 10.1002/PMIC.200600506
I Muegge, T Schweins, R Langen, A Warshel, Electrostatic control of GTP and GDP binding in the oncoprotein p21ras Structure. ,vol. 4, pp. 475- 489 ,(1996) , 10.1016/S0969-2126(96)00052-4
Nicola Normanno, Sabine Tejpar, Floriana Morgillo, Antonella De Luca, Eric Van Cutsem, Fortunato Ciardiello, Implications for KRAS status and EGFR-targeted therapies in metastatic CRC Nature Reviews Clinical Oncology. ,vol. 6, pp. 519- 527 ,(2009) , 10.1038/NRCLINONC.2009.111
G Smith, R Bounds, H Wolf, R J C Steele, F A Carey, C R Wolf, Activating K-Ras mutations outwith 'hotspot' codons in sporadic colorectal tumours - implications for personalised cancer medicine. British Journal of Cancer. ,vol. 102, pp. 693- 703 ,(2010) , 10.1038/SJ.BJC.6605534
M Horsch, C V Recktenwald, S Schädler, M Hrabé de Angelis, B Seliger, J Beckers, Overexpressed vs mutated Kras in murine fibroblasts: a molecular phenotyping study British Journal of Cancer. ,vol. 100, pp. 656- 662 ,(2009) , 10.1038/SJ.BJC.6604882
M. Peeters, J.Y. Douillard, E. Van Cutsem, S. Siena, K. Zhang, R. Williams, J. Wiezorek, Evaluation of Individual Codon 12 and 13 Mutant (MT) KRAS Alleles as Prognostic and Predictive Biomarkers of Response to Panitumumab (pmab) in Patients with Metastatic Colorectal Cancer (mCRC) European Journal of Cancer. ,vol. 47, pp. 16- ,(2011) , 10.1016/S0959-8049(11)70132-0